P521: TREATMENT OF BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM IN PEDIATRIC PATIENTS WITH TAGRAXOFUSP, A CD123-TARGETED THERAPY
Authors: N. Pemmaraju, B. Cuglievan, J. Lasky, A. Kheradpour, N. Hijiya, A. S. Stein, S. Meshinchi, C. Mullen, E. Angelucci, L. Vinti, T. I. Mughal, A. Pawlowska
Journal: HemaSphere (2022)

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy derived from plasmacytoid dendritic cell precursors that overexpress CD123, the interleukin-3 receptor alpha. Though primarily a disease of the elderly, BPDCN has been documented in infants and children in 10–20% of all cases. The rarity of BPDCN in the pediatric population makes collecting robust safety and efficacy data challenging and there is a paucity of data published for pediatric patients (pts). A first-in-class, CD123-directed therapy, tagraxofusp (TAG, SL-401) is the only approved treatment for patients with BPDCN. A multicohort prospective study (NCT02113982) demonstrated a tolerable safety profile and a durable overall response rate of 75% (median duration 24.9 months) in first-line (1L) pts. TAG is approved by the US FDA for the treatment of BPDCN in pts over the age of 2 years with newly diagnosed and relapsed or refractory (R/R) BPDCN; it is also approved by the EMA for 1L treatment of adult pts. Herein, we present a case series of pediatric pts with BPDCN treated with TAG, to provide further insight into the efficacy and safety of this therapy in this understudied patient population. Aims: To expand on the body of data regarding TAG therapy in pediatric pts with BPDCN. Methods: Pediatric case reports of BPDCN were collected from centers across the US and Europe. TAG was administered according to local institutional guidelines 1L, or R/R. Data was collated and summarized descriptively. Analyses included tumor response, survival, and safety (adverse events [AEs] and laboratory values). Results: Eight pediatric pts with BPDCN were treated with TAG and included in this analysis. Median age was 15.5 years (range 2 – 21 years), and 7 of the 8 pts were female. Five pts were treatment naïve, and 3 pts were R/R. Four pts had skin only disease. Two pts had skin, bone marrow (BM), and lymph node (LN) involvement; 1 of these also had central nervous system (CNS) involvement. One patient had BM and LN, but no skin involvement, and 1 patient had BM only disease. A 2-year-old patient received 7 mcg/kg TAG in combination with venetoclax and azacitidine at second relapse; all other pts received 12 mcg/kg throughout all treatment cycles. The number of TAG cycles administered ranged from 1 to 4 at the time of data cutoff. A decrease in albumin occurred in 2 pts, and 2 pts had a rise in transaminases, all of which were manageable. One patient experienced headaches, hot flashes, fatigue, and mouth sores. One patient experienced grade 2 capillary leak syndrome in cycle 1, which was treated and resolved, and the patient went on to receive subsequent cycles. No AEs were seen in 3 pts. Three 1L pts achieved a complete response, including 1 patient with extensive disease (skin, bone marrow, and CNS) who also received intrathecal therapy. One 1L and 1 R/R patient achieved stable disease (no progression after 4 TAG cycles each), and 1 patient with R/R BPDCN progressed while on TAG. Five pts treated with TAG were bridged to a stem cell transplant (n=3 1L, n=2 R/R; Table 1). Median survival data will be presented (6 of 8 pts remain alive). Image:Summary/Conclusion: These cases expand the knowledge base of BPDCN treatment in pediatric pts. TAG was well tolerated in all pts, with a manageable safety profile that was similar to that reported for adults in the pivotal study. Treatment with TAG demonstrated promising efficacy, with responses that enabled 5 of 8 pediatric pts, including 3 1L and 2 R/R, to be bridged to stem cell transplant.